These studies propose to systematically define and characterize the fundamental immunologic properties (both humoral and cellular) of the lung. The studies are designed to test the hypotheses: (a) that the respiratory tract can function as an immunologically competent organ, and (b) that the pulmonary and the systemic immune systems function to some degree independently. The principal investigator has previously characterized the functional properties of bronchoalveolar lymphocytes obtained by lavage of the normal dog lung. Baseline data have been obtained demonstrating the primary antibody-forming cell (Jerne plaque assay) response of multiple canine lymphoid tissues (bronchoalveolar cells, hilar and peripheral lymph nodes, spleen and blood leukocytes) after either intravenous or intrapulmonary immunization with sheep erythrocytes. This project proposes to extend these observations to include a study of the distribution of radiolabelled sheep cells, to explore the effects of antigens of differing physicochemical properties, to examine the secondary antibody-forming cell response of the lung, and to study cell-mediated immune reactions of the lower respiratory tract as a function of the immunization route. In addition, the secretory antibody system will be examined at various levels of the respiratory tract to determine the degree of difference in class-specific immunoglobulin content in comparison with those of serum. The effect of environmental manipulation on the response of the lung to intrapulmonary and systemically applied antigens will be explored. These studies of the inherent immune capabilities and limitations of the lung will provide basic and new information which will allow a better understanding of the host-defense functions and the immunopathogenic mechanisms occurring in the respiratory tract.